Crystal structure and functional characterization of the complement regulator mannose-binding lectin (MBL)/ficolin-associated protein-1 (MAP-1).
The human lectin complement pathway activation molecules comprise mannose-binding lectin (MBL) and ficolin-1, -2, and -3 in complex with associated serine proteases MASP-1, -2, and -3 and the non-enzymatic small MBL associated protein or sMAP. Recently, a novel plasma protein named MBL/ficolin-assoc...
| Những tác giả chính: | , , , , , , , |
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| Định dạng: | Journal article |
| Ngôn ngữ: | English |
| Được phát hành: |
2012
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| _version_ | 1826274078630084608 |
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| author | Skjoedt, M Roversi, P Hummelshøj, T Palarasah, Y Rosbjerg, A Johnson, S Lea, S Garred, P |
| author_facet | Skjoedt, M Roversi, P Hummelshøj, T Palarasah, Y Rosbjerg, A Johnson, S Lea, S Garred, P |
| author_sort | Skjoedt, M |
| collection | OXFORD |
| description | The human lectin complement pathway activation molecules comprise mannose-binding lectin (MBL) and ficolin-1, -2, and -3 in complex with associated serine proteases MASP-1, -2, and -3 and the non-enzymatic small MBL associated protein or sMAP. Recently, a novel plasma protein named MBL/ficolin-associated protein-1 (MAP-1) was identified in humans. This protein is the result of a differential splicing of the MASP1 gene and includes the major part of the heavy chain but lacks the serine protease domain. We investigated the direct interactions of MAP-1 and MASP-3 with ficolin-3 and MBL using surface plasmon resonance and found affinities around 5 nm and 2.5 nm, respectively. We studied structural aspects of MAP-1 and could show by multi-angle laser light scattering that MAP-1 forms a calcium-dependent homodimer in solution. We were able to determine the crystal structure of MAP-1, which also contains a head-to-tail dimer ∼146 Å long. This structure of MAP-1 also enables modeling and assembly of the MASP-1 molecule in its entirety. Finally we found that MAP-1 competes with all three MASPs for ligand binding and is able to mediate a strong dose-dependent inhibitory effect on the lectin pathway activation, as measured by levels of C3 and C9. |
| first_indexed | 2024-03-06T22:37:59Z |
| format | Journal article |
| id | oxford-uuid:5a93f299-b45c-4f79-8a6d-a6ab0cae27a5 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:37:59Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:5a93f299-b45c-4f79-8a6d-a6ab0cae27a52022-03-26T17:16:30ZCrystal structure and functional characterization of the complement regulator mannose-binding lectin (MBL)/ficolin-associated protein-1 (MAP-1).Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5a93f299-b45c-4f79-8a6d-a6ab0cae27a5EnglishSymplectic Elements at Oxford2012Skjoedt, MRoversi, PHummelshøj, TPalarasah, YRosbjerg, AJohnson, SLea, SGarred, PThe human lectin complement pathway activation molecules comprise mannose-binding lectin (MBL) and ficolin-1, -2, and -3 in complex with associated serine proteases MASP-1, -2, and -3 and the non-enzymatic small MBL associated protein or sMAP. Recently, a novel plasma protein named MBL/ficolin-associated protein-1 (MAP-1) was identified in humans. This protein is the result of a differential splicing of the MASP1 gene and includes the major part of the heavy chain but lacks the serine protease domain. We investigated the direct interactions of MAP-1 and MASP-3 with ficolin-3 and MBL using surface plasmon resonance and found affinities around 5 nm and 2.5 nm, respectively. We studied structural aspects of MAP-1 and could show by multi-angle laser light scattering that MAP-1 forms a calcium-dependent homodimer in solution. We were able to determine the crystal structure of MAP-1, which also contains a head-to-tail dimer ∼146 Å long. This structure of MAP-1 also enables modeling and assembly of the MASP-1 molecule in its entirety. Finally we found that MAP-1 competes with all three MASPs for ligand binding and is able to mediate a strong dose-dependent inhibitory effect on the lectin pathway activation, as measured by levels of C3 and C9. |
| spellingShingle | Skjoedt, M Roversi, P Hummelshøj, T Palarasah, Y Rosbjerg, A Johnson, S Lea, S Garred, P Crystal structure and functional characterization of the complement regulator mannose-binding lectin (MBL)/ficolin-associated protein-1 (MAP-1). |
| title | Crystal structure and functional characterization of the complement regulator mannose-binding lectin (MBL)/ficolin-associated protein-1 (MAP-1). |
| title_full | Crystal structure and functional characterization of the complement regulator mannose-binding lectin (MBL)/ficolin-associated protein-1 (MAP-1). |
| title_fullStr | Crystal structure and functional characterization of the complement regulator mannose-binding lectin (MBL)/ficolin-associated protein-1 (MAP-1). |
| title_full_unstemmed | Crystal structure and functional characterization of the complement regulator mannose-binding lectin (MBL)/ficolin-associated protein-1 (MAP-1). |
| title_short | Crystal structure and functional characterization of the complement regulator mannose-binding lectin (MBL)/ficolin-associated protein-1 (MAP-1). |
| title_sort | crystal structure and functional characterization of the complement regulator mannose binding lectin mbl ficolin associated protein 1 map 1 |
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